Fascinating Furanosteroids and Their Pharmacological Profile

This review article delves into the realm of furanosteroids and related isoprenoid lipids derived from diverse terrestrial and marine sources, exploring their wide array of biological activities and potential pharmacological applications. Fungi, fungal endophytes, plants, and various marine organisms, including sponges, corals, molluscs, and other invertebrates, have proven to be abundant reservoirs of these compounds. The biological activities exhibited by furanosteroids and related lipids encompass anticancer, cytotoxic effects against various cancer cell lines, antiviral, and antifungal effects. Notably, the discovery of exceptional compounds such as nakiterpiosin, malabaricol, dysideasterols, and cortistatins has revealed their potent anti-tuberculosis, antibacterial, and anti-hepatitis C attributes. These compounds also exhibit activity in inhibiting protein kinase C, phospholipase A2, and eliciting cytotoxicity against cancer cells. This comprehensive study emphasizes the significance of furanosteroids and related lipids as valuable natural products with promising therapeutic potential. The remarkable biodiversity found in both terrestrial and marine ecosystems offers an extensive resource for unearthing novel biologically active compounds, paving the way for future drug development and advancements in biomedical research. This review presents a compilation of data obtained from various studies conducted by different authors who employed the PASS software 9.1 to evaluate the biological activity of natural furanosteroids and compounds closely related to them. The utilization of the PASS software in this context offers valuable advantages, such as screening large chemical libraries, identifying compounds for subsequent experimental investigations, and gaining insights into potential biological activities based on their structural features. Nevertheless, it is crucial to emphasize that experimental validation remains indispensable for confirming the predicted activities.

Furanosteroids represent a class of pentacyclic isoprenoid lipids that are synthesized by fungi and various other organisms. These compounds possess additional fused furan, dihydrofuran, or tetrahydrofuran ring(s) attached to their pentacyclic backbone [8][9][10].
Initially, furanosteroids were identified in mushrooms nearly 80 years ago, characterized by the presence of an extra furan ring connecting positions 4 and 6 of the steroid skeleton. However, the term "furanosteroids" has since been expanded to include any steroids and related compounds that contain the furan ring, 2,3-dihydrofuran ring, 2,5-dihydrofuran ring, and/or tetrahydrofuran ring (s). It is believed that the strained furan cycle contributes to the diverse biological activities exhibited by these compounds. Several metabolites belonging to this class of natural products have garnered significant attention in pharmacological research due to their potent anti-inflammatory and antibiotic properties, potential anti-proliferative activity, and ability to inhibit inositide-3-kinase [8,9,[11][12][13][14].
This review is dedicated to furanosteroids and related isoprenoid lipids, their occurrence in fungi, plants, and marine organisms, and the exploration of their biological activity.
An unusual steroid compound, 1,11-epoxy-3-hydroxy-methylenecycloartan-28-oic acid (17), was isolated from an unidentified fungus [36]. Similar steroid structures have been identified in species belonging to the Agaricaceae family. Notably, a series of rare 1,11-epoxy lanostane-type triterpenoids called lepiotaprocerins A-F (18)(19)(20)(21)(22)(23) were isolated from the fruiting bodies of the edible mushroom Macrolepiota procera collected in Poland. These compounds exhibited significant inhibitory effects on nitric oxide production, outperforming the positive control, L-NG-monomethyl arginine [37].  (a) Trichoderma viride is a fungus or mold that reproduces asexually through spores. The mycelium of this fungus can produce various enzymes, such as cellulases and chitinases. These enzymes are involved in the degradation of cellulose and chitin, respectively. Trichoderma viride commonly grows on wood, which predominantly consists of cellulose, as well as on fungi whose cell walls are primarily composed of chitin. It exhibits a parasitic nature towards the mycelium and fruiting bodies of other fungi, including cultivated ones. The fungus is known to cause "Green mold fungus disease" [38,39]. (b) Hymenoscyphus pseudoalbidus, also known as the Ash Wax Moth, is a saprotrophic fungus. It can be found growing on decaying trunks and branches of ash trees. The fruiting bodies of this fungus are hardly distinguishable from a macroscopic or microscopic perspective. It is commonly observed on the same substrate [40,41]. (a) Trichoderma viride is a fungus or mold that reproduces asexually through spores. The mycelium of this fungus can produce various enzymes, such as cellulases and chitinases. These enzymes are involved in the degradation of cellulose and chitin, respectively. Trichoderma viride commonly grows on wood, which predominantly consists of cellulose, as well as on fungi whose cell walls are primarily composed of chitin. It exhibits a parasitic nature towards the mycelium and fruiting bodies of other fungi, including cultivated ones. The fungus is known to cause "Green mold fungus disease" [38,39]. (b) Hymenoscyphus pseudoalbidus, also known as the Ash Wax Moth, is a saprotrophic fungus. It can be found growing on decaying trunks and branches of ash trees. The fruiting bodies of this fungus are hardly distinguishable from a macroscopic or microscopic perspective. It is commonly observed on the same substrate [40,41].

Figure 5. (a) Talaromyces marneffei:
Talaromyces is a genus of fungi belonging to the family Trichocomaceae. It was first described in 1955 by the American mycologist Chester Ray Benjamin, who specialized in the taxonomy of fungal molds in the Eurotiales and Mucorales orders. Talaromyces marneffei, previously known as Penicillium marneffei, was identified in 1956. This fungus is endemic to Southeast Asia and is a significant cause of opportunistic infections in individuals with immunodeficiency associated with HIV/AIDS [42,43]. (b) Penicillium funiculosum: P. funiculosum is a plant pathogenic fungus that infects pineapple fruits. The disease it causes is referred to as fruit core rot, which is characterized by the browning or blackening and rotting of the fruit's core [44,45]. (c) Fusarium oxysporum: F. oxysporum is an ascomycete fungus belonging to the family Nectriaceae. F. oxysporum strains are commonly found in soil and can exist as saprophytes, deriving nutrients from decaying organic matter. They are capable of degrading lignin and complex carbohydrates present in soil residues [46,47].
Endophytic fungi originating from Astragalus species were found to catalyze the biotransformation of cycloastragenol, leading to the synthesis of an uncommon meroterpenoid compound 24 [48]. Additionally, through the utilization of an Astragalus endophyte called Alternaria eureka 1E1BL1, the biotransformation of cyclocephagenol, a novel cycloartane-type sapogenin with a tetrahydropyran unit, resulted in the formation of rare metabolites (25)(26)(27). The structures of these metabolites are depicted in Figure 7 [49]. Talaromyces is a genus of fungi belonging to the family Trichocomaceae. It was first described in 1955 by the American mycologist Chester Ray Benjamin, who specialized in the taxonomy of fungal molds in the Eurotiales and Mucorales orders. Talaromyces marneffei, previously known as Penicillium marneffei, was identified in 1956. This fungus is endemic to Southeast Asia and is a significant cause of opportunistic infections in individuals with immunodeficiency associated with HIV/AIDS [42,43]. (b) Penicillium funiculosum: P. funiculosum is a plant pathogenic fungus that infects pineapple fruits. The disease it causes is referred to as fruit core rot, which is characterized by the browning or blackening and rotting of the fruit's core [44,45]. (c) Fusarium oxysporum: F. oxysporum is an ascomycete fungus belonging to the family Nectriaceae. F. oxysporum strains are commonly found in soil and can exist as saprophytes, deriving nutrients from decaying organic matter. They are capable of degrading lignin and complex carbohydrates present in soil residues [46,47].
Endophytic fungi originating from Astragalus species were found to catalyze the biotransformation of cycloastragenol, leading to the synthesis of an uncommon meroterpenoid compound 24 [48]. Additionally, through the utilization of an Astragalus endophyte called Alternaria eureka 1E1BL1, the biotransformation of cyclocephagenol, a novel cycloartanetype sapogenin with a tetrahydropyran unit, resulted in the formation of rare metabolites (25)(26)(27). The structures of these metabolites are depicted in Figure 7 [49]. The graph demonstrates a high confidence level of over 94% in the activity predictions. According to the data from Table 1, the dominant activity of steroids 7, 8, and 10 in the graph is shown in red. The steroid wortmanolone (7) is an antineoplastic and inositol-3-kinase inhibitor. The steroid wortmannin A (8) is an inositol-4-kinase inhibitor and inositol-3-kinase inhibitor of activity, and steroid secovironolide (10) is an inositol-4-kinase inhibitor and inositol-3-kinase inhibitor of activity. The activity text is in red for the steroid wortmanolone; in black is the activity of the steroid wortmannin A; and in blue is the activity of the steroid secovironolide. Red color-strong activity, blue colorno activity.
Trichocitrin (48), a diterpene, was extracted from the alga-endophytic fungus Trichoderma citrinoviride. Its structure is depicted in Figure 9, and the biological activity is outlined in Table 3. This compound represents the first furan-bearing fusicoccane diterpene derived from Trichoderma sp. and has shown inhibitory effects against E. coli [60]. The fungus Aspergillus ustus, isolated from the Mediterranean sponge Suberites domuncula, produced the sesterterpenoids ophiobolin-types 49 and 50 [61].
Two phytotoxic sesterterpenoids, namely ophiobolin A lactone (51) and B (52), are synthesized by Pseudomonas aeruginosa, while compound 52 is also produced by the Figure 6. Three-dimensional graph illustrates the predicted and calculated activity as inositol-3kinase inhibitors for steroids 7, 8, and 10 produced by the endophytic fungus Talaromyces wortmannii. The graph demonstrates a high confidence level of over 94% in the activity predictions. According to the data from Table 1, the dominant activity of steroids 7, 8, and 10 in the graph is shown in red. The steroid wortmanolone (7) is an antineoplastic and inositol-3-kinase inhibitor. The steroid wortmannin A (8) is an inositol-4-kinase inhibitor and inositol-3-kinase inhibitor of activity, and steroid secovironolide (10) is an inositol-4-kinase inhibitor and inositol-3-kinase inhibitor of activity. The activity text is in red for the steroid wortmanolone; in black is the activity of the steroid wortmannin A; and in blue is the activity of the steroid secovironolide. Red color-strong activity, blue color-no activity.
Tricholumin A (67) was obtained from the alga-endophytic fungus Trichoderma asperellum. It retains cycle A, the final structural element of the original ergosterol, after undergoing deep oxidative transformations in the rest of the molecule, including the side chain fragment [35].
Tricholumin A (67) was obtained from the alga-endophytic fungus Trichoderma asperellum. It retains cycle A, the final structural element of the original ergosterol, after undergoing deep oxidative transformations in the rest of the molecule, including the side chain fragment [35].
Agaricus blazei (a picture of this fungus is shown in Figure 12), also known as 'Cogumelo do Sol' in Brazil or 'Himematsutake' in Japan, is a widely cultivated mushroom with medicinal uses.
A triterpenoid named irpexolidal (97) with an unprecedented carbon skeleton, along with its biogenetic-related compound irpexolide A (98) were isolated from the fruiting bodies of the medicinal fungus Irpex lacteus [91]. Study of the extract of the fruiting bodies of the mushroom Leucopaxillus gentianeus, allowed the isolation of minor cucurbitane triterpene, leucopaxillone B (99, the 3D graph is shown in Figure 13). The antiproliferative activity of the isolated triterpene was determined against the NCI-H460 human tumour cell line [92]. Simplifusidic acids B (100) and D (101), fusidane-type nortriterpenoids, were isolated from the marine-derived fungus Simplicillium sp. SCSIO 41513 [93]. Bioactive compounds 83-99, known as withaphysalins, were isolated from Physalis minima. These compounds typically possess a hemiacetal or lactone linkage between C-18 and C-20, and they have demonstrated cytotoxic, antiproliferative, and anti-inflammatory activities [86,87].
Agaricus blazei (a picture of this fungus is shown in Figure 12), also known as 'Cogumelo do Sol' in Brazil or 'Himematsutake' in Japan, is a widely cultivated mushroom with medicinal uses.
A triterpenoid named irpexolidal (97) with an unprecedented carbon skeleton, along with its biogenetic-related compound irpexolide A (98) were isolated from the fruiting bodies of the medicinal fungus Irpex lacteus [91]. Study of the extract of the fruiting bodies of the mushroom Leucopaxillus gentianeus, allowed the isolation of minor cucurbitane triterpene, leucopaxillone B (99, the 3D graph is shown in Figure 13). The antiproliferative activity of the isolated triterpene was determined against the NCI-H460 human tumour cell line [92]. Simplifusidic acids B (100) and D (101), fusidane-type nortriterpenoids, were isolated from the marine-derived fungus Simplicillium sp. SCSIO 41513 [93].  This ascomycete fungus typically thrives on dead wood and is known for producing steroids (68). The genus Xylaria comprises fungal endophytes associated with both vascular and non-vascular plants, and it serves as a valuable source of bioactive secondary metabolites. These metabolites include sesquiterpenoids, esters, alcohols, terpenoids, cytochalasins, mellein, alkaloids, polyketides, and aromatic compounds. Some of these compounds have demonstrated potential activity as herbicides, fungicides, insecticides, antibacterials, antimalarials, antifungals, or αglucosidase inhibitors [94]. (b) Agaricus blazei: This medicinal fungus contains secosteroids (90)(91)(92)(93)(94)(95). With significant commercial value, Agaricus blazei offers a wide range of health benefits. The mushrooms are rich in biologically active substances such as polysaccharides, lipids, sterols, proteins, vitamins B, C, and D, as well as phenolic compounds. Polysaccharides from A. blazei have been shown to possess immunoregulatory, anti-inflammatory, hepatoprotective, and antitumor properties. Extracts from this fungus have been used to treat diabetes and bacterial infections, exhibiting anticarcinogenic and antimutagenic effects [95,96]. (c) Irpex lacteus: This medicinal fungus serves as a source of triterpenoids (97 and 98). Irpex lacteus, a white rot fungus, is widely employed in bioremediation and food biotechnology due to its exceptional lignin-degrading capabilities. The fungus produces various extracellular enzymes, including lignin peroxidase, laccase, glucose oxidase, proteases, and α-galactosidase, involved in oxidative, hydrolytic, and lignocellulose degradation processes. Irpex lacteus readily oxidizes steroids, triterpenoids, alkanes, and cyclic ketones [97,98]. This ascomycete fungus typically thrives on dead wood and is known for producing steroids (68). The genus Xylaria comprises fungal endophytes associated with both vascular and non-vascular plants, and it serves as a valuable source of bioactive secondary metabolites. These metabolites include sesquiterpenoids, esters, alcohols, terpenoids, cytochalasins, mellein, alkaloids, polyketides, and aromatic compounds. Some of these compounds have demonstrated potential activity as herbicides, fungicides, insecticides, antibacterials, antimalarials, antifungals, or α-glucosidase inhibitors [94]. (b) Agaricus blazei: This medicinal fungus contains secosteroids (90)(91)(92)(93)(94)(95). With significant commercial value, Agaricus blazei offers a wide range of health benefits. The mushrooms are rich in biologically active substances such as polysaccharides, lipids, sterols, proteins, vitamins B, C, and D, as well as phenolic compounds. Polysaccharides from A. blazei have been shown to possess immunoregulatory, anti-inflammatory, hepatoprotective, and antitumor properties. Extracts from this fungus have been used to treat diabetes and bacterial infections, exhibiting anticarcinogenic and antimutagenic effects [95,96]. (c) Irpex lacteus: This medicinal fungus serves as a source of triterpenoids (97 and 98). Irpex lacteus, a white rot fungus, is widely employed in bioremediation and food biotechnology due to its exceptional lignin-degrading capabilities. The fungus produces various extracellular enzymes, including lignin peroxidase, laccase, glucose oxidase, proteases, and α-galactosidase, involved in oxidative, hydrolytic, and lignocellulose degradation processes. Irpex lacteus readily oxidizes steroids, triterpenoids, alkanes, and cyclic ketones [97,98]. Figure 13. Three-dimensional graph illustrating the predicted and calculated antineoplastic activity of steroids (74, 75, and 99) with a confidence level exceeding 91%. These steroids are derived from meroterpenoids produced by the fungus Physalis angulata, while the steroid is sourced from the mushroom Leucopaxillus gentianeus.
The leaves of Trichilia gilgiana, extracted with CH 2 Cl 2 -MeOH, yielded vilasinin-type limonoids known as rubescin H (105), gilgianin A (106), gilgianin B (107), TS3 (108), and trichirubine A (109). Furanosteroids 105, 106, and 107 demonstrated potent anti-plasmodial activity alongside significant cytotoxicity. Compounds 108 and 109 exhibited the highest anti-plasmodial activity, with IC 50 values of 1.1 and 1.3 µM, respectively [106]. The structures of compounds 105, 106, and 107 are shown in Figure 15, and their biological activity is detailed in Table 5. Furthermore, a 3D graph illustrating the activity of compounds 108 and 109 is displayed in Figure 16. Native to Madagascar, the Comoros, and Aldabra, plants in the Meliaceae family are known to contain limonoids, terpenoids, alkaloids, flavonoids, and phenolic compounds as their primary chemical constituents. Many species within this family exhibit cytotoxic, antimicrobial, or antimalarial activity [107]. (b) Azadirachta indica (Neem): Azadirachta indica, commonly known as Neem, belongs to the Meliaceae family. The leaves of Neem are widely used in Chinese, Ayurvedic, and Unani medicines, particularly in the Indian subcontinent. Neem leaves have demonstrated antibacterial, anthelmintic, antiviral, and anticancer properties, and most notably, they act as an immunomodulatory agent [108]. (c) Annona squamosa (Sugar Apple): Annona squamosa, also known as sugar apple, is a member of the Annonaceae family. It has been traditionally used in Indian, Thai, and American medicine. The leaves of sugar apple are commonly used as a decoction to treat dysentery and urinary tract infections [109].
Azadirachta indica, belonging to the family Meliaceae, is commonly known as neem or Indian lilac. It is utilized for its antimalarial, anti-inflammatory, antipyretic, antitumor, and anthelmintic properties. The leaves of Azadirachta indica contain tetranortriterpenoids such as 110 and 111 [110].
Sutherlandia frutescens, a plant from the Fabaceae family native to South Africa, is commonly referred to as Cancer bush. It is renowned for its multifunctional medicinal uses, and infusions and decoctions of the plant are widely employed in South Africa for treating cancer, inflammation, viral infections, and gastrointestinal diseases. An unusual cycloartane glycoside called sutherlandioside A (112) has been isolated from the watermethanol fraction of the plant [111]. Azadirachta indica, belonging to the family Meliaceae, is commonly known as neem or Indian lilac. It is utilized for its antimalarial, anti-inflammatory, antipyretic, antitumor, and anthelmintic properties. The leaves of Azadirachta indica contain tetranortriterpenoids such as 110 and 111 [110].
Sutherlandia frutescens, a plant from the Fabaceae family native to South Africa, is commonly referred to as Cancer bush. It is renowned for its multifunctional medicinal uses, and infusions and decoctions of the plant are widely employed in South Africa for treating cancer, inflammation, viral infections, and gastrointestinal diseases. An unusual cycloartane glycoside called sutherlandioside A (112) has been isolated from the watermethanol fraction of the plant [111]. Chisocheton paniculatus twigs yielded two tetranortriterpenoids named chisonimbolinins A (113) and F (114) [112]. Furthermore, a triterpenoid 115 with insecticidal activity was isolated from a methanol extract of fresh leaves of Azadirachta indica [113]. Chisocheton paniculatus twigs yielded two tetranortriterpenoids named chisonimbolinins A (113) and F (114) [112]. Furthermore, a triterpenoid 115 with insecticidal activity was isolated from a methanol extract of fresh leaves of Azadirachta indica [113].
A tetranortriterpenoid called kokosanolide D (131) has been isolated from the methanol extract of fruit peels of Lansium domesticum, found in West Java, Indonesia [120]. Furthermore, an ethanol extract of a plant belonging to the Malleastrum genus yielded three steroids known as malleastrones A-C (132, 133, and 134), respectively. Compounds 133 and 134 exhibited antiproliferative activity against a range of cancer cell lines, with IC50 values ranging from 0.19 to 0.63 μM [121,122]. Figure 16. Three-dimensional graph illustrates the predicted and calculated antiprotozoal (Plasmodium) activity of the vilasinin-type limonoids (106, 107, 108, and 109) with a confidence level exceeding 95%. These limonoids are derived from the tree Trichilia gilgiana, which is predominantly found in southern Nigeria and eastern Congo. In the Congo region, the extract of Trichilia gilgiana bark is utilized for its analgesic and stimulant properties. It has been traditionally used in traditional medicine to treat abdominal pain, chest pain, fever, and as a tonic. The juice of the young leaves is applied to circumcised wounds, while crushed leaves are added to drinking water for the treatment of respiratory diseases. Additionally, the juice of the leaves has demonstrated potent activity against the malarial Plasmodium [123][124][125]. Figure 16. Three-dimensional graph illustrates the predicted and calculated antiprotozoal (Plasmodium) activity of the vilasinin-type limonoids (106, 107, 108, and 109) with a confidence level exceeding 95%. These limonoids are derived from the tree Trichilia gilgiana, which is predominantly found in southern Nigeria and eastern Congo. In the Congo region, the extract of Trichilia gilgiana bark is utilized for its analgesic and stimulant properties. It has been traditionally used in traditional medicine to treat abdominal pain, chest pain, fever, and as a tonic. The juice of the young leaves is applied to circumcised wounds, while crushed leaves are added to drinking water for the treatment of respiratory diseases. Additionally, the juice of the leaves has demonstrated potent activity against the malarial Plasmodium [123][124][125]. Limbocinin (135) and compound 136 were isolated from ethanolic extracts of neem seeds and the leaves of Azadirachta indica and Annona squamosa [126,127]. Both compounds exhibited antifungal activity [128].
Two limonoids with an aromatic ring D, walsucochinoids A (140) and B (141) were detected in the air-dried plant Walsura cochinchinensis (Figure 18 depicts a picture of this plant). Limbocinin (135) and compound 136 were isolated from ethanolic extracts of neem seeds and the leaves of Azadirachta indica and Annona squamosa [126,127]. Both compounds exhibited antifungal activity [128].
Two limonoids with an aromatic ring D, walsucochinoids A (140) and B (141) were detected in the air-dried plant Walsura cochinchinensis (Figure 18 depicts a picture of this plant). Studies have identified over 200 compounds from ten species within this genus, including sesquiterpenoids, flavonoids, sterols, lignans, xanthones, and anthraquinones. Many of these compounds exhibit diverse properties such as cancer cell cytotoxicity, antimicrobial activity, antidiabetic effects, anti-inflammatory effects, antioxidant properties, antifeedant properties, antifertility effects, ichthyotoxic effects, and neuroprotective effects [134,135]. (b) Gynostemma pentaphyllum: Also known as Jiaogulan, Gynostemma pentaphyllum is a dioecious climbing vine from the Cucurbitaceae family. It is widely distributed in South and East Asia, as well as New Guinea. In Chinese medicine, it is commonly used to treat various conditions, including hepatitis, diabetes, and cardiovascular diseases. Extracts from G. pentaphyllum contain sterols, flavonoids, and polysaccharides that exhibit inhibitory activity against cancer cell proliferation. These extracts have demonstrated effects such as cell cycle arrest, apoptosis induction, inhibition of invasion and metastasis, inhibition of glycolysis, and immunomodulatory activity [136,137]. (c) Momordica charantia: The fruit of M. charantia, which contains anticancer steroids (147 and 148), has been consumed as food and used as medicine since ancient times. M. charantia, commonly known as bitter melon, holds a significant place in various systems of traditional medicine. It has been used to treat a wide range of conditions, including diabetes, abortive purposes, anthelmintic effects, contraception, dysmenorrhea, eczema, emmenagogue properties, antimalarial activity, lactagogue effects, gout, jaundice, abdominal pain, renal issues (stones), laxative effects, leprosy, leucorrhea, hemorrhoids, pneumonia, psoriasis, rheumatism, fever, and scabies [138,139]. Studies have identified over 200 compounds from ten species within this genus, including sesquiterpenoids, flavonoids, sterols, lignans, xanthones, and anthraquinones. Many of these compounds exhibit diverse properties such as cancer cell cytotoxicity, antimicrobial activity, antidiabetic effects, anti-inflammatory effects, antioxidant properties, antifeedant properties, antifertility effects, ichthyotoxic effects, and neuroprotective effects [134,135]. (b) Gynostemma pentaphyllum: Also known as Jiaogulan, Gynostemma pentaphyllum is a dioecious climbing vine from the Cucurbitaceae family. It is widely distributed in South and East Asia, as well as New Guinea. In Chinese medicine, it is commonly used to treat various conditions, including hepatitis, diabetes, and cardiovascular diseases. Extracts from G. pentaphyllum contain sterols, flavonoids, and polysaccharides that exhibit inhibitory activity against cancer cell proliferation. These extracts have demonstrated effects such as cell cycle arrest, apoptosis induction, inhibition of invasion and metastasis, inhibition of glycolysis, and immunomodulatory activity [136,137]. (c) Momordica charantia: The fruit of M. charantia, which contains anticancer steroids (147 and 148), has been consumed as food and used as medicine since ancient times. M. charantia, commonly known as bitter melon, holds a significant place in various systems of traditional medicine. It has been used to treat a wide range of conditions, including diabetes, abortive purposes, anthelmintic effects, contraception, dysmenorrhea, eczema, emmenagogue properties, antimalarial activity, lactagogue effects, gout, jaundice, abdominal pain, renal issues (stones), laxative effects, leprosy, leucorrhea, hemorrhoids, pneumonia, psoriasis, rheumatism, fever, and scabies [138,139].
From the leaves of Caloncoba glauca, a triterpenoid called caloncobalactone C (142) was isolated. It exhibited inhibitory activity against human and mouse 11β-hydroxysteroid dehydrogenase types 1 and 2 [140,141]. The 3D graph illustrating its structure is presented in Figure 19. From the leaves of Caloncoba glauca, a triterpenoid called caloncobalactone C (142) was isolated. It exhibited inhibitory activity against human and mouse 11β-hydroxysteroid dehydrogenase types 1 and 2 [140,141]. The 3D graph illustrating its structure is presented in Figure 19. Within the EtOAc and n-BuOH extracts of the vines and leaves of Momordica aurantia, two steroids, octanorcucurbitacin (143) and kuguacin I (144), were discovered. These compounds demonstrated anti-HIV-1 activities in vitro [142]. Triterpenes gypensapogenin H (145) and I (146) were isolated from the hydrolyzate of the total saponin extract obtained from the dioecious herbaceous climber Gynostemma pentaphyllum, which is widely distributed in South and East Asia [143].
The roots of Cimicifuga heracleifolia, a plant included in the Chinese Pharmacopoeia and used in traditional medicine in China for centuries, contain two unusual ring A cracking 9,19-cycloartane triterpenes (149) and (150) [145]. The dried fruit of Vitex negundo yielded the 3,10-epoxide (151) with antitumor activity [146].
From the seeds of Hovenia trichocarpa, two saponins named hoduloside XI and hoduloside XII were isolated. Both compounds shared the genin 20,26-epoxy-pseudojujubogenin (152) and displayed inhibitive activities against human cancer cell lines HL-60 and K562 [147]. In addition to these steroids, a furanosteroid named ceramicine J (153) was discovered in the hexane layer of Chisocheton ceramicus bark extract. This compound exhibited dose-dependent, moderate cytotoxicity against the HL-60 cell line [148]. Within the EtOAc and n-BuOH extracts of the vines and leaves of Momordica aurantia, two steroids, octanorcucurbitacin (143) and kuguacin I (144), were discovered. These compounds demonstrated anti-HIV-1 activities in vitro [142]. Triterpenes gypensapogenin H (145) and I (146) were isolated from the hydrolyzate of the total saponin extract obtained from the dioecious herbaceous climber Gynostemma pentaphyllum, which is widely distributed in South and East Asia [143].
The roots of Cimicifuga heracleifolia, a plant included in the Chinese Pharmacopoeia and used in traditional medicine in China for centuries, contain two unusual ring A cracking 9,19-cycloartane triterpenes (149) and (150) [145]. The dried fruit of Vitex negundo yielded the 3,10-epoxide (151) with antitumor activity [146].
The steroid inertogenin (155) is a compound containing a rare 7,15-tetrahydrofuran group. It is found in the leaves of Strophanthus amboensis, an erect deciduous shrub harvested for medical use in Southwest Africa [149]. The structure of inertogenin is depicted in Figure 20, and its biological activity is shown in Table 7. The leaves of Toona ciliata var. yunnanensis yielded several seco steroids: tooonayunnanins F (156), G (157), J (158), and K (159) [150].
Steroidal alkaloids, solasodine (167), and tomatidine (168) were isolated from the aerial parts of Solanum leucocarpum, a plant belonging to the Solanaceae family. The collection was made at the regional natural park Ucumarí in Colombia. Both alkaloids have demonstrated biological activity. Solasodine exhibits DNA-damaging activity, while tomatidine displays activity through DNA topoisomerase II inhibition [155].
The roots and stems of Cyathula officinalis, also known as Cyathula Root or Radix Cyathula, yielded two cyasterone stereoisomers: 28-epi-cyasterone (176) and 25-epi-28-epicyasterone (177) [159]. The biologically active plant steroid, 28-epi-cyasterone (176), has also been found in Eriophyton wallchii [160] and fronds of the fern Microsorum scolopendria [161].    (160)(161)(162)(163)(164). F. pallidiflora, also known as Siberian hazel grouse, is a species that was initially misnamed as it does not grow wild in Siberia. It was discovered in 1857 in the western regions of the Himalayas and Asia Minor. The plant is known for its medicinal uses, and an infusion of dried chopped onion from this plant is commonly used orally to treat cough, bronchitis, pneumonia, febrile illnesses, and abscesses [162,163]. Shaanxi fir (b) is a tree that grows in Gansu, Hubei, and Sichuan. Abies chensiensis, a species of Shaanxi fir, produces unusual triterpenoids (169 and 170). The essential oil of Shaanxi fir, as well as Siberian fir (Abies sibirica), has a pleasant, fresh pine aroma and contains bornyl acetate, which contributes to its soothing, balancing, and anti-inflammatory effects. The oil is used to relieve anger, promote contentment, alleviate intolerance in toxic relationships, promote self-connection, and foster a fearless attitude [164,165]. The pericarps of Zanthoxylum bungeanum (c) produce an unusual steroid (175). Extracts from Z. bungeanum fruit are widely used in the cosmetics industry to produce creams. Various parts of this plant, including the fruit, stems, leaves, and bark, have been utilized in local medical systems to treat fever, stomach pain, toothache, and inflammation [166,167].
Triterpenoids with medicinal properties have been identified from various plant sources. Abinukitrine A (178), a triterpenoid, was isolated from Abies nukiangensis extracts and exhibited a potent anti-hepatitis C virus (HCV) effect [62]. Malabaricol (179), another triterpenoid, was first reported by Indian chemists from the National Chemical Laboratory in 1967, isolated from the tropical tree Ailanthus malabarica [168]. Subsequently, malabaricol (179) and 180 were also found in the heartwood of Ailanthus excelsa [169]. Malabaricol and its derivatives [170] possess antibacterial effects, supporting their traditional use in folk medicine [171]. Ailanthus triphysa is a source of ailanthusins F (181) and G (182) [172], while two other derivatives, 183 and 184, were discovered in the leaves of Caloncoba echinata [173].
Furthermore, triterpene glycosides called taimordisins A (185) and B (186) were isolated from the fresh fruits of Taiwanese Momordica charantia [174]. Although these compounds demonstrate favorable anti-inflammatory activity, they do not exhibit any anticancer properties and have been determined to be safe for use.  (160)(161)(162)(163)(164). F. pallidiflora, also known as Siberian hazel grouse, is a species that was initially misnamed as it does not grow wild in Siberia. It was discovered in 1857 in the western regions of the Himalayas and Asia Minor. The plant is known for its medicinal uses, and an infusion of dried chopped onion from this plant is commonly used orally to treat cough, bronchitis, pneumonia, febrile illnesses, and abscesses [162,163]. Shaanxi fir (b) is a tree that grows in Gansu, Hubei, and Sichuan. Abies chensiensis, a species of Shaanxi fir, produces unusual triterpenoids (169 and 170). The essential oil of Shaanxi fir, as well as Siberian fir (Abies sibirica), has a pleasant, fresh pine aroma and contains bornyl acetate, which contributes to its soothing, balancing, and anti-inflammatory effects. The oil is used to relieve anger, promote contentment, alleviate intolerance in toxic relationships, promote self-connection, and foster a fearless attitude [164,165]. The pericarps of Zanthoxylum bungeanum (c) produce an unusual steroid (175). Extracts from Z. bungeanum fruit are widely used in the cosmetics industry to produce creams. Various parts of this plant, including the fruit, stems, leaves, and bark, have been utilized in local medical systems to treat fever, stomach pain, toothache, and inflammation [166,167].
Triterpenoids with medicinal properties have been identified from various plant sources. Abinukitrine A (178), a triterpenoid, was isolated from Abies nukiangensis extracts and exhibited a potent anti-hepatitis C virus (HCV) effect [62]. Malabaricol (179), another triterpenoid, was first reported by Indian chemists from the National Chemical Laboratory in 1967, isolated from the tropical tree Ailanthus malabarica [168]. Subsequently, malabaricol (179) and 180 were also found in the heartwood of Ailanthus excelsa [169]. Malabaricol and its derivatives [170] possess antibacterial effects, supporting their traditional use in folk medicine [171]. Ailanthus triphysa is a source of ailanthusins F (181) and G (182) [172], while two other derivatives, 183 and 184, were discovered in the leaves of Caloncoba echinata [173].
Furthermore, triterpene glycosides called taimordisins A (185) and B (186) were isolated from the fresh fruits of Taiwanese Momordica charantia [174]. Although these compounds demonstrate favorable anti-inflammatory activity, they do not exhibit any anti-cancer properties and have been determined to be safe for use. Figure 22. Three-dimensional graph illustrating the predicted and calculated anti-tuberculosis activity of steroids (160, 161, 162, 163, and 164) with a confidence level exceeding 90%. These steroids include the unusual steroidal jervinine-type alkaloids (160)(161)(162)(163) derived from the bulbs of Fritillaria pallidiflora, as well as alkaloid (164) obtained from the bulbs of Fritillaria puqiensis. Notably, these compounds possess the rare property of exhibiting anti-tuberculosis activity. The genus Fritillaria has been widely used worldwide for medicinal and culinary purposes. For over 2000 years, decoctions made from the bulbs of various Fritillaria species have been utilized in traditional Chinese medicine to address diverse ailments such as asthma, pharyngitis, bronchitis, coughs, goiter, and hemoptysis. Additionally, it has been employed as an expectorant and antitussive agent [175,176].
Unusual steroids known as erylosides T (195) and U (196), derived from the sea sponge Erylus goffrilleri, contain novel genins [182]. Lanostanes (197 and 198), whose structures are depicted in Figure 24 and whose biological activity is presented in Table 8, were obtained from the marine sponge Penares sp., found in Vietnamese waters [183]. These  (160, 161, 162, 163, and 164) with a confidence level exceeding 90%. These steroids include the unusual steroidal jervinine-type alkaloids (160)(161)(162)(163) derived from the bulbs of Fritillaria pallidiflora, as well as alkaloid (164) obtained from the bulbs of Fritillaria puqiensis. Notably, these compounds possess the rare property of exhibiting anti-tuberculosis activity. The genus Fritillaria has been widely used worldwide for medicinal and culinary purposes. For over 2000 years, decoctions made from the bulbs of various Fritillaria species have been utilized in traditional Chinese medicine to address diverse ailments such as asthma, pharyngitis, bronchitis, coughs, goiter, and hemoptysis. Additionally, it has been employed as an expectorant and antitussive agent [175,176].
Unusual steroids known as erylosides T (195) and U (196), derived from the sea sponge Erylus goffrilleri, contain novel genins [182]. Lanostanes (197 and 198), whose structures are depicted in Figure 24 and whose biological activity is presented in Table 8, were obtained from the marine sponge Penares sp., found in Vietnamese waters [183]. These discoveries highlight the diverse range of bioactive compounds originating from marine sources.
Molecules 2023, 27, x FOR PEER REVIEW 37 of 52 of lanostanes (197 and 198). These diverse marine organisms contribute to the production of biologically active compounds with potential pharmacological applications. The marine sponge Hippospongia sp. collected from Taitung, Taiwan, serves as the source of a cytotoxic metabolite called hippospongide A (210) [191], as depicted in the 3D graph shown in Figure 25. Furthermore, the same compound, named salmahyrtisol A (211), has been isolated from the marine sponge Hyrtios erecta and exhibits significant cytotoxicity against murine leukemia (P-388), A-549, and HT-29 human cancer cells [192]. The marine sponge Hippospongia sp. collected from Taitung, Taiwan, serves as the source of a cytotoxic metabolite called hippospongide A (210) [191], as depicted in the 3D graph shown in Figure 25. Furthermore, the same compound, named salmahyrtisol A (211), has been isolated from the marine sponge Hyrtios erecta and exhibits significant cytotoxicity against murine leukemia (P-388), A-549, and HT-29 human cancer cells [192]. These findings underscore the potential of marine sponges as a valuable source of bioactive compounds with cytotoxic properties. These findings underscore the potential of marine sponges as a valuable source of bioactive compounds with cytotoxic properties. Figure 25. Three-dimensional graph illustrates the predicted and calculated antineoplastic activity of steroids (210, 218, 219, 220, and 221) with a confidence level exceeding 92%. These cytotoxic, highly polyoxygenated steroids are isolated from marine organisms inhabiting the waters surrounding Taiwan. Specifically, a metabolite (210) is found in the marine sponge Hippospongia sp., while the bamboo coral Isis hippuris contains compounds (218)(219)(220)(221). These discoveries highlight the potential of marine organisms to provide valuable bioactive compounds with antineoplastic properties.
Steroidal anticancer alkaloids known as cortistatins A (212), B (213), C (214), and D (215) have been isolated from the marine sponge Corticium simplex. These alkaloids possess a unique 9 (10-19)-abeo-androstane and isoquinoline skeleton and have demonstrated the ability to inhibit the proliferation of human umbilical vein endothelial cells with high selectivity [193].
Metabolites containing the core structure of viridin have been extracted from marine invertebrates. Over 40 years ago, a research group led by Paul Scheuer at the University of Hawaii at Mānoa isolated demethoxyviridin (4) and its furano-quinone analogue called halenaquinone (216) from the marine sponge Xestospongia exigua [194]. Raspacionin A (217), a triterpenoid, was obtained from the red sponge Raspaciona aculeata found in the Mediterranean Sea. This compound exhibited cytotoxicity against the MCF-7 tumor cell line, with an IC50 value of 4 μM [195][196][197]. Highly polyoxygenated steroids (218-221) containing three or four additional tetrahydrofuran fragments were discovered in the bamboo coral Isis hippuris, collected from the Southeast coast of Taiwan. These steroids displayed cytotoxic activity against Hep G2, Hep 3B, A549, MCF-7, and MDAMB-231 cells [198]. Additionally, two steroids (222 and 223), whose structures are depicted in Figure 26 and whose biological activity is presented in Table 9, were isolated from the soft coral Sarcophyton crassocaula found in the Indian Ocean [199]. Furthermore, the cytotoxic compound sinubrasone B (224) was identified in the reef soft coral Sinularia brassica [200].  218, 219, 220, and 221) with a confidence level exceeding 92%. These cytotoxic, highly polyoxygenated steroids are isolated from marine organisms inhabiting the waters surrounding Taiwan. Specifically, a metabolite (210) is found in the marine sponge Hippospongia sp., while the bamboo coral Isis hippuris contains compounds (218)(219)(220)(221). These discoveries highlight the potential of marine organisms to provide valuable bioactive compounds with antineoplastic properties.
Steroidal anticancer alkaloids known as cortistatins A (212), B (213), C (214), and D (215) have been isolated from the marine sponge Corticium simplex. These alkaloids possess a unique 9 (10-19)-abeo-androstane and isoquinoline skeleton and have demonstrated the ability to inhibit the proliferation of human umbilical vein endothelial cells with high selectivity [193].
Metabolites containing the core structure of viridin have been extracted from marine invertebrates. Over 40 years ago, a research group led by Paul Scheuer at the University of Hawaii at Mānoa isolated demethoxyviridin (4) and its furano-quinone analogue called halenaquinone (216) from the marine sponge Xestospongia exigua [194]. Raspacionin A (217), a triterpenoid, was obtained from the red sponge Raspaciona aculeata found in the Mediterranean Sea. This compound exhibited cytotoxicity against the MCF-7 tumor cell line, with an IC 50 value of 4 µM [195][196][197]. Highly polyoxygenated steroids (218)(219)(220)(221) containing three or four additional tetrahydrofuran fragments were discovered in the bamboo coral Isis hippuris, collected from the Southeast coast of Taiwan. These steroids displayed cytotoxic activity against Hep G2, Hep 3B, A549, MCF-7, and MDAMB-231 cells [198]. Additionally, two steroids (222 and 223), whose structures are depicted in Figure 26 and whose biological activity is presented in Table 9, were isolated from the soft coral Sarcophyton crassocaula found in the Indian Ocean [199]. Furthermore, the cytotoxic compound sinubrasone B (224) was identified in the reef soft coral Sinularia brassica [200]. Crellastatin A (225), a unique nonsymmetric dimeric steroid, was isolated from the marine sponge Crella sp. found on Vanuatu Island. This compound showcases an unprecedented connection through its side chains. Crellastatin A has been shown to possess significant in vitro cytotoxic activity against NSCLC-N6 cells, with an IC50 value of 0.5 μM [201]. This discovery underscores the potential of marine organisms to produce novel bioactive compounds with cytotoxic properties.
A similar dimeric steroid derivative, shishicrellastatin A (226), has been isolated from the marine sponge Crella (Yvesia) spinulata. This compound functions as a cathepsin B inhibitor, exhibiting an IC50 value of 8 μg/mL [202]. Another dimeric steroid, amaroxocane B (227), was discovered in the Caribbean coral reef sponge Phorbas amaranthus collected off Key Largo, Florida. It has shown effectiveness as an antifeedant [203]. Additionally, the same sterol dimer, hamigerol B (227), has been identified in the extract of the Mediterranean sponge Hamigera hamigera [204].
Furthermore, a sulfated sterol dimer named fibrosterol C (228), obtained from Lissodendoryx (Acanthodoryx) fibrosa collected in the Philippines, has been found to inhibit protein kinase Cζ with an IC50 value of 5.6 μM [205]. The 3D graph illustrating its activity is shown in Figure 27. Cephalostatin 20 (229), a member of the cephalostatin family known for its anticancer properties, has been isolated as a minor component of extracts from the marine worm Cephalodiscus gilchristi [206]. A picture of this sea sponge is displayed in Figure 28. Crellastatin A (225), a unique nonsymmetric dimeric steroid, was isolated from the marine sponge Crella sp. found on Vanuatu Island. This compound showcases an unprecedented connection through its side chains. Crellastatin A has been shown to possess significant in vitro cytotoxic activity against NSCLC-N6 cells, with an IC 50 value of 0.5 µM [201]. This discovery underscores the potential of marine organisms to produce novel bioactive compounds with cytotoxic properties.
A similar dimeric steroid derivative, shishicrellastatin A (226), has been isolated from the marine sponge Crella (Yvesia) spinulata. This compound functions as a cathepsin B inhibitor, exhibiting an IC 50 value of 8 µg/mL [202]. Another dimeric steroid, amaroxocane B (227), was discovered in the Caribbean coral reef sponge Phorbas amaranthus collected off Key Largo, Florida. It has shown effectiveness as an antifeedant [203]. Additionally, the same sterol dimer, hamigerol B (227), has been identified in the extract of the Mediterranean sponge Hamigera hamigera [204].
Furthermore, a sulfated sterol dimer named fibrosterol C (228), obtained from Lissodendoryx (Acanthodoryx) fibrosa collected in the Philippines, has been found to inhibit protein kinase Cζ with an IC 50 value of 5.6 µM [205]. The 3D graph illustrating its activity is shown in Figure 27. Cephalostatin 20 (229), a member of the cephalostatin family known for its anticancer properties, has been isolated as a minor component of extracts from the marine worm Cephalodiscus gilchristi [206]. A picture of this sea sponge is displayed in Figure 28. . Three-dimensional graph presents the predicted and calculated activity of the steroid (228) with a confidence level exceeding 92%. This steroid is recognized as a protein kinase C inhibitor and exhibits potential as an anticancer and antiviral agent. It is a sulfated sterol dimer found in the marine sponge Lissodendoryx (Acanthodoryx) fibrosa, which belongs to the family Coelosphaeridae. This marine sponge is commonly found in the oceanic waters of the Philippines. The discovery of this compound highlights its promising bioactive properties derived from marine sources.   (228) with a confidence level exceeding 92%. This steroid is recognized as a protein kinase C inhibitor and exhibits potential as an anticancer and antiviral agent. It is a sulfated sterol dimer found in the marine sponge Lissodendoryx (Acanthodoryx) fibrosa, which belongs to the family Coelosphaeridae. This marine sponge is commonly found in the oceanic waters of the Philippines. The discovery of this compound highlights its promising bioactive properties derived from marine sources.
Molecules 2023, 27, x FOR PEER REVIEW 40 of 52 Figure 27. Three-dimensional graph presents the predicted and calculated activity of the steroid (228) with a confidence level exceeding 92%. This steroid is recognized as a protein kinase C inhibitor and exhibits potential as an anticancer and antiviral agent. It is a sulfated sterol dimer found in the marine sponge Lissodendoryx (Acanthodoryx) fibrosa, which belongs to the family Coelosphaeridae. This marine sponge is commonly found in the oceanic waters of the Philippines. The discovery of this compound highlights its promising bioactive properties derived from marine sources. The marine sponge Isis hippuris serves as a source of steroids (202) and (203). (c) The marine sponge Corticium simplex produces steroidal alkaloids (212)(213)(214)(215). (d) The marine worm Cephalodiscus gilchristi synthesizes a unique steroidal alkaloid (229). These diverse marine organisms contribute to the production of bioactive compounds with potential pharmacological applications. The marine sponge Isis hippuris serves as a source of steroids (202) and (203). (c) The marine sponge Corticium simplex produces steroidal alkaloids (212)(213)(214)(215).
(d) The marine worm Cephalodiscus gilchristi synthesizes a unique steroidal alkaloid (229). These diverse marine organisms contribute to the production of bioactive compounds with potential pharmacological applications.
Sednolide (237) and sednolide 22-acetate (238) were identified in extracts of the nudibranch Chromodoris sedna, collected in Baja California (Mexico). A picture of this mollusc is displayed in Figure 29. Sednolide (237) demonstrated growth inhibition of the marine bacterium Vibrio anguillarum at a concentration of 100 µg/disk [211].
Sednolide (237) and sednolide 22-acetate (238) were identified in extracts of the nudibranch Chromodoris sedna, collected in Baja California (Mexico). A picture of this mollusc is displayed in Figure 29. Sednolide (237) demonstrated growth inhibition of the marine bacterium Vibrio anguillarum at a concentration of 100 μg/disk [211]. A rare and unusual aminosteroid called clionamine D (239), with its structure shown in Figure 30 and biological activity presented in Table 10, has been isolated from South African specimens of the sponge Cliona celata. This aminosteroid possesses a unique spiro bis-lactone side chain and exhibits cytotoxicity. It also modulates autophagy [212]. A rare and unusual aminosteroid called clionamine D (239), with its structure shown in Figure 30 and biological activity presented in Table 10, has been isolated from South African specimens of the sponge Cliona celata. This aminosteroid possesses a unique spiro bis-lactone side chain and exhibits cytotoxicity. It also modulates autophagy [212].  Isomalabaricane-type triterpenoids, namely globostelletins P (240) and Q (241), have been isolated from the marine sponge Rhabdastrella globostellata. These triterpenoids, along with the CH 2 Cl 2 fraction of the sponge, demonstrate inhibitory activities against various human tumor cell lines, including A549 (human lung adenocarcinoma), BGC-823 (human gastric carcinoma), HCT-8 (colonic carcinoma), Bel-7402 (human liver carcinoma), and A2780 (human ovarian carcinoma) [213].
A series of steroids known as sinubrasolides A-F (246-251), which belong to the class of withanolide-type steroids, were isolated from cultured specimens of Sinularia brassica from Taiwan [216]. Petrosaspongiolides A (252) and B (253) were the first cheilantane sesterterpene lactones to be isolated from a New Caledonian sponge initially assigned to the genus Dactylospongia but later reclassified as a new genus and species called Petrosaspongia nigra [217,218]. Additionally, other petrosasponiolides, namely M (254) and R (255), isolated from the New Caledonian marine sponge Petrosaspongia nigra, exhibited a γ-hydroxybutenolide moiety and a hemiacetal function [219,220]. The 3D graph illustrating the activity of compound 255 is shown in Figure 31. Isomalabaricane-type triterpenoids, namely globostelletins P (240) and Q (241), have been isolated from the marine sponge Rhabdastrella globostellata. These triterpenoids, along with the CH2Cl2 fraction of the sponge, demonstrate inhibitory activities against various human tumor cell lines, including A549 (human lung adenocarcinoma), BGC-823 (human gastric carcinoma), HCT-8 (colonic carcinoma), Bel-7402 (human liver carcinoma), and A2780 (human ovarian carcinoma) [213].
A series of steroids known as sinubrasolides A-F (246-251), which belong to the class of withanolide-type steroids, were isolated from cultured specimens of Sinularia brassica from Taiwan [216]. Petrosaspongiolides A (252) and B (253) were the first cheilantane sesterterpene lactones to be isolated from a New Caledonian sponge initially assigned to the genus Dactylospongia but later reclassified as a new genus and species called Petrosaspongia nigra [217,218]. Additionally, other petrosasponiolides, namely M (254) and R (255), isolated from the New Caledonian marine sponge Petrosaspongia nigra, exhibited a γ-hydroxybutenolide moiety and a hemiacetal function [219,220]. The 3D graph illustrating the activity of compound 255 is shown in Figure 31. Cytotoxic steroids named kiheisterones A (256) and B (257) have been isolated from a sponge of the order Poecilosclerida collected along the coast of the island of Maui (Hawaii). These sterols possess an α,β-disubstituted furan in the sidechain, a cis-fused A/B ring, a monoenolized α-di-ketone in the A ring, and a C-21 carboxyl group. Both steroids exhibit mild cytotoxicity against several human tumor cell lines, including A-549 lung Cytotoxic steroids named kiheisterones A (256) and B (257) have been isolated from a sponge of the order Poecilosclerida collected along the coast of the island of Maui (Hawaii). These sterols possess an α,β-disubstituted furan in the sidechain, a cis-fused A/B ring, a monoenolized α-di-ketone in the A ring, and a C-21 carboxyl group. Both steroids exhibit mild cytotoxicity against several human tumor cell lines, including A-549 lung carcinoma, HT-29 colon adenocarcinoma, and the P-388 murine lymphocytic leukemia cell line [220]. Furthermore, cytotoxic sesterterpenoids named inorolide A (258), B (259), and C (260) have been isolated from the Japanese nudibranch Chromodoris inornata (Chromodorididae) [221].
A sarcosterol derivative, 22,25-epoxy-23,24-dimethylcholesta-5,17(20)-dien-3-ol (264), has been discovered in the soft coral Sinularia mayi [224]. Additionally, the soft coral Lobophytum depressum contains two steroids: lobophytosterol (265), which is a 22,28epoxyergost-5-ene-3,25,28-triol, and 5,6-epoxy-lobophytosterol (266). A picture of this soft coral is displayed in Figure 32 [225,226]. Both steroids possess a double bond at positions 5,6. Lobophytosterol from the soft coral Lobophytum laevigatum has demonstrated cytotoxicity against A549 and HL-60 cell lines, with IC50 values of 4.5 and 5.6 μM, respectively [227].  (240 and 241). (d) The marine mollusc Spisula sachalinensis contains the steroid (243). S. sachalinensis is a bivalve mollusc found in the Sea of Japan and the Sea of Okhotsk, inhabiting medium-to fine-grained sands at depths ranging from 0.5 to 10 m. It is the largest of the molluscs, reaching a length of approximately 130 mm and weighing around 500 g. This mollusc is considered a delicacy and is actively fished in Japan and Primorsky Krai (Russia) [228].  (240 and 241). (d) The marine mollusc Spisula sachalinensis contains the steroid (243). S. sachalinensis is a bivalve mollusc found in the Sea of Japan and the Sea of Okhotsk, inhabiting medium-to fine-grained sands at depths ranging from 0.5 to 10 m. It is the largest of the molluscs, reaching a length of approximately 130 mm and weighing around 500 g. This mollusc is considered a delicacy and is actively fished in Japan and Primorsky Krai (Russia) [228].

Conclusions
This comprehensive review examines the occurrence of furanosteroids and related isoprenoid lipids in various sources, including fungi, plants, and marine organisms. It provides an in-depth analysis of their biological activity, shedding light on their potential applications and significance in drug discovery. Furanosteroids and related isoprenoid lipids have garnered significant attention due to their diverse biological properties. This review aims to explore the occurrence of these compounds in fungi, plants, and marine organisms, as well as delve into their associated biological activity. By analyzing their medicinal and pharmacological potential, this review highlights the importance of furanosteroids as promising natural products for future research and development. The biological activity of furanosteroids and related isoprenoid lipids constitutes a crucial aspect of their investigation. This review focuses on the diverse range of activities exhibited by these compounds, including but not limited to anti-inflammatory, anticancer, and antimicrobial properties.